We propose to continue our "team" approach to five areas of investigation: 1. Factors controlling phosphate excretion will be studies using clearance, micropuncture and metabolic balance studies to assess: sites of transport, interrelationships with Na and Ca handling, mechanism of action parathyroid hormone (PTH) and other agents, role of Na independent and/or glucose-related P transport, changes in P excretion as "marker" of proximal transport. Factors controlling Ca excretion will be studied to evaluate nephron sites of regulation, Na dependent and Na independent systems, Ca transport mechanisms in distal nephron, effects of PTH, drugs, glucose, acidosis; Ca excretion as a "marker" for changes in distal transport. 2. Pathogenesis of Analgesic Abuse Nephropathy will be studied by physiological, biochemical and ultrastructural methods to test the hypothesis that oxidative damage to lipid membranes is due to metabolites of phenacetin, potentiated by inhibition of the tissue defenses against such damage by salicylate. 3. Regulation of water excretion will be studied in normal man and in patients with impaired water excretion to evaluate importance of physiological volume changes in ADH and role of ADH in hyponatremic conditions using radio-immunoassay of vasopressin, balance and clearance techniques. The toad bladder will be used to evaluate mechanisms of transport abnormalities in drug-induced nephrogenic diabetes insipidus. 4. The role of intermediate molecular weight species (e.g., "natriuretic factor") in uremic man will be studied using ultrafiltration-dialysis (diafiltration) in vivo and toad bladder assays in vitro. 5. Pathophysiology of Renal Tubular Acidosis in man will be studied in clearance and balance methods, assessing the roles of potassium depletion and hyperparathyroidism in producing alterations in proximal tubular transport of bicarbonate, and the significance of urinary PCO2 as an index of altered distal permeability to hydrogen ion.